The etiologic agents of Lyme disease are species of the Borrelia burgdorferi sensu latu complex. Lyme Disease represents a significant health threat with over 10,000 cases being reported each year in the United States. Several outer surface proteins (Osps) have been identified in these bacteria and these are now the major focus of vaccine and diagnostic assay development. The Lyme Disease spirochetes (LDS), which cause chronic infection in mammals, utilize undefined mechanisms to avoid being eliminated by host defense systems. The closely related relapsing fever Borrelia possesses a plasmid carried vmp gene family (variable membrane proteins) that play a central role in immune evasion through antigenic variation. Antigenic diversity in these bacteria is generated by a variety of mechanisms. Antigenic variation allows these bacteria to survive for weeks to months in the mammalian host before they are cleared. In the LDS we have identified a family of genes, related to OspE and F (also carried by the LDS), that exhibit important similarities to the vmp genes of the relapsing fever spirochetes. The ospEF gene family members have highly similar 5' upstream sequences or upstream homology boxes (UHB) that contain a putative transcriptional promoter and also carry a downstream homology block (DHB). The central regions of these genes exhibit significant variation in sequence, with some variants apparently generated by recombinational events. It is our hypothesis that this gene family is used by the Lyme Disease spirochetes to generate antigenic variation, although in a less subtle way than the relapsing fever spirochetes, to avoid being destroyed by the host's defense systems and to maintain chronic infection. The objectives of this study are to identify and characterize the ospEF gene family. The expression patterns of these genes will be determined and the antibody response to them in experimentally infected animals and human Lyme Disease patients will be defined.